Showing papers in "American Journal of Psychiatry in 2009"

Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Individuals With Major Depressive Disorder

Abstract: Objective: Major depressive disorder is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional MRI (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that individuals with major depression would show reduced reward-related responses in basal ganglia structures. Method: A monetary incentive delay task was presented to 30 unmedicated individuals with major depressive disorder and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to rewardpredicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes. Results: Relative to comparison subjects, participants with major depression showed significantly weaker responses to gains in the left nucleus accumbens and the caudate bilaterally. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in the major depression group emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although participants with major depression showed reduced activation to reward cues in a small sector of the left posterior putamen. In the major depression group, anhedonic symptoms and depression severity were associated with reduced caudate volume bilaterally. Conclusions: These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.

Randomized controlled trial of outpatient mentalization-based treatment versus structured clinical management for borderline personality disorder

Abstract: Objective: This randomized controlled trial tested the effectiveness of an 18-month mentalization-based treatment (MBT) approach in an outpatient context against a structured clinical management (SCM) outpatient approach for treatment of borderline personality disorder. Method: Patients (N=134) consecutively referred to a specialist personality disorder treatment center and meeting selection criteria were randomly allocated to MBT or SCM. Eleven mental health professionals equal in years of experience and training served as therapists. Independent evaluators blind to treatment allocation conducted assessments every 6 months. The primary outcome was the occurrence of crisis events, a composite of suicidal and severe self-injurious behaviors and hospitalization. Secondary outcomes included social and interpersonal functioning and self-reported symptoms. Outcome measures, assessed at 6-month intervals, were analyzed using mixed effects logistic regressions for binary data, Poisson regression models for count...

Transdiagnostic Cognitive-Behavioral Therapy for Patients With Eating Disorders: A Two-Site Trial With 60-Week Follow-Up

Abstract: Objective: The aim of this study was to compare two cognitive-behavioral treatments for outpatients with eating disorders, one focusing solely on eating disorder features and the other a more complex treatment that also addresses mood intolerance, clinical perfectionism, low self-esteem, or interpersonal difficulties. Method: A total of 154 patients who had a DSM-IV eating disorder but were not markedly underweight (body mass index over 17.5), were enrolled in a two-site randomized controlled trial involving 20 weeks of treatment and a 60-week closed period of follow-up. The control condition was an 8-week waiting list period preceding treatment. Outcomes were measured by independent assessors who were blind to treatment condition. Results: Patients in the waiting list control condition exhibited little change in symptom severity, whereas those in the two treatment conditions exhibited substantial and equivalent change, which was well maintained during follow-up. At the 60-week follow-up assessment, 51.3% of the sample had a level of eating disorder features less than one standard deviation above the community mean. Treatment outcome did not depend on eating disorder diagnosis. Patients with marked mood intolerance, clinical perfectionism, low self-esteem, or interpersonal difficulties appeared to respond better to the more complex treatment, with the reverse pattern evident among the remaining patients. Conclusions: These two transdiagnostic treatments appear to be suitable for the majority of outpatients with an eating disorder. The simpler treatment may best be viewed as the default version, with the more complex treatment reserved for patients with marked additional psychopathology of the type targeted by the treatment.

Psychiatric Disorders and Repeat Incarcerations: The Revolving Prison Door

Abstract: Objective: A number of legal, social, and political factors over the past 40 years have led to the current epidemic of psychiatric disorders in the U.S. prison system. Although numerous investigations have reported substantially elevated rates of psychiatric disorders among prison inmates compared with the general population, it is unclear whether mental illness is a risk factor for multiple episodes of incarceration. The authors examined this association in a retrospective cohort study of the nation’s largest state prison system. Method: The study population included 79,211 inmates who began serving a sentence between September 1, 2006, and August 31, 2007. Data on psychiatric disorders, demographic characteristics, and history of incarceration for the preceding 6-year period were obtained from statewide medical information systems and analyzed. Results: Inmates with major psychiatric disorders (major depressive disorder, bipolar disorders, schizophrenia, and nonschizophrenic psychotic disorders) had sub...

Amygdala Hypoactivity to Fearful Faces in Boys With Conduct Problems and Callous-Unemotional Traits

Abstract: Objective: Although early-onset conduct problems predict both psychiatric and health problems in adult life, little research has been done to index neural correlates of conduct problems. Emerging research suggests that a subgroup of children with conduct problems and elevated levels of callous-unemotional traits may be genetically vulnerable to manifesting disturbances in neural reactivity to emotional stimuli indexing distress. Using functional MRI, the authors evaluated differences in neural response to emotional stimuli between boys with conduct problems and elevated levels of callous-unemotional traits and comparison boys. Method: Seventeen boys with conduct problems and elevated levels of callous-unemotional traits and 13 comparison boys of equivalent age (mean=11 years) and IQ (mean=100) viewed blocked presentations of fearful and neutral faces. For each face, participants distinguished the sex of the face via manual response. Results: Relative to the comparison group, boys with conduct problems and...

Increased mortality in bulimia nervosa and other eating disorders

Abstract: Objective: Anorexia nervosa has been consistently associated with increased mortality, but whether this is true for other types of eating disorders is unclear. The goal of this study was to determine whether anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified are associated with increased all-cause mortality or suicide mortality. Method: Using computerized record linkage to the National Death Index, the authors conducted a longitudinal assessment of mortality over 8 to 25 years in 1,885 individuals with anorexia nervosa (N=177), bulimia nervosa (N=906), or eating disorder not otherwise specified (N=802) who presented for treatment at a specialized eating disorders clinic in an academic medical center. Results: Crude mortality rates were 4.0% for anorexia nervosa, 3.9% for bulimia nervosa, and 5.2% for eating disorder not otherwise specified. All-cause standardized mortality ratios were significantly elevated for bulimia nervosa and eating disorder not otherwise specified; suicid...

A randomized trial of dialectical behavior therapy versus general psychiatric management for borderline personality disorder.

Abstract: Objective: The authors sought to evaluate the clinical efficacy of dialectical behavior therapy compared with general psychiatric management, including a combination of psychodynamically informed therapy and symptom-targeted medication management derived from specific recommendations in APA guidelines for borderline personality disorder. Method: This was a single-blind trial in which 180 patients diagnosed with borderline personality disorder who had at least two suicidal or nonsuicidal self-injurious episodes in the past 5 years were randomly assigned to receive 1 year of dialectical behavior therapy or general psychiatric management. The primary outcome measures, assessed at baseline and every 4 months over the treatment period, were frequency and severity of suicidal and nonsuicidal self-harm episodes. Results: Both groups showed improvement on the majority of clinical outcome measures after 1 year of treatment, including significant reductions in the frequency and severity of suicidal and nonsuicidal ...

Altered Striatal Activation Predicting Real-World Positive Affect in Adolescent Major Depressive Disorder

Abstract: Objective: Alterations in reward-related brain function and phenomenological aspects of positive affect are increasingly examined in the development of major depressive disorder. The authors tested differences in reward-related brain function in healthy and depressed adolescents, and the authors examined direct links between reward-related brain function and positive mood that occurred in real-world contexts. Method: Fifteen adolescents with major depressive disorder and 28 adolescents with no history of psychiatric disorder, ages 8–17 years, completed a functional magnetic resonance imaging guessing task involving monetary reward. Participants also reported their subjective positive affect in natural environments during a 4-day cell-phone-based ecological momentary assessment. Results: Adolescents with major depressive disorder exhibited less striatal response than healthy comparison adolescents during reward anticipation and reward outcome, but more response in dorsolateral and medial prefrontal cortex....

Childhood IQ and Adult Mental Disorders: A Test of the Cognitive Reserve Hypothesis

Abstract: Objective: Cognitive reserve has been proposed as important in the etiology of neuropsychiatric disorders. However, tests of the association between premorbid IQ and adult mental disorders other than schizophrenia have been limited and inconclusive. The authors tested the hypothesis that low childhood IQ is associated with increased risk and severity of adult mental disorders. Method: Participants were members of a representative 1972–1973 birth cohort of 1,037 males and females in Dunedin, New Zealand, who were followed up to age 32 with 96% retention. WISC-R IQ was assessed at ages 7, 9, and 11. Research diagnoses of DSM mental disorders were made at ages 18, 21, 26, and 32. Results: Lower childhood IQ was associated with increased risk of developing schizophrenia spectrum disorder, adult depression, and adult anxiety. Lower childhood IQ was also associated with greater comorbidity and with persistence of depression; the association with persistence of generalized anxiety disorder was nearly significant...

Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials.

Abstract: Objective: The authors sought to determine by meta-analysis the efficacy and tolerability of adjunctive atypical antipsychotic agents in major depressive disorder. Method: Searches were conducted of MEDLINE/PubMed (1966 to January 2009), the Cochrane database, abstracts of major psychiatric meetings since 2000, and online trial registries. Manufacturers of atypical antipsychotic agents without online registries were contacted. Trials selected were acute-phase, parallel-group, double-blind controlled trials with random assignment to adjunctive atypical antipsychotic or placebo. Patients had nonpsychotic unipolar major depressive disorder that was resistant to prior antidepressant treatment. Response, remission, and discontinuation rates were either reported or obtained. Data were extracted by one author and checked by the second. Data included study design, number of patients, patient characteristics, methods of establishing treatment resistance, drug doses, duration of the adjunctive trial, depression sca...

A Meta-Analysis of Head-to-Head Comparisons of Second-Generation Antipsychotics in the Treatment of Schizophrenia

Abstract: Objective: Whether there are differences in efficacy among second-generation antipsychotics in the treatment of schizophrenia is a matter of heated debate. The authors conducted a systematic review and meta-analysis of blinded studies comparing second-generation antipsychotics head-to-head. Method: Searches of the Cochrane Schizophrenia Group’s register (May 2007) and MEDLINE (September 2007) were conducted for randomized, blinded studies comparing two or more of nine second-generation antipsychotics in the treatment of schizophrenia. All data were extracted by at least three reviewers independently. The primary outcome measure was change in total score on the Positive and Negative Syndrome Scale; secondary outcome measures were positive and negative symptom subscores and rate of dropout due to inefficacy. The results were combined in a meta-analysis. Various sensitivity analyses and metaregressions were used to examine bias. Results: The analysis included 78 studies with 167 relevant arms and 13,558 part...

Genomewide association studies: history, rationale, and prospects for psychiatric disorders.

Abstract: Objective: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. Method: A literature review was carried out, power and other issues discussed, and planned studies assessed. Results: Most of the genomic DNA sequence differences between any two people are common (frequency >5%) single nucleotide polymorphisms (SNPs). Because of localized patterns of correlation (linkage disequilibrium), 500,000 to 1,000,000 of these SNPs can test the hypothesis that one or more common variants explain part of the genetic risk for a disease. GWAS technologies can also detect some of the copy number variants (deletions and duplications) in the genome. Systematic study of rare variants will require large-scale resequencing analyses. GWAS methods have detected a remarkable number of robust genetic associations for dozens of common diseases and traits, leading to new pathophysiological hypotheses, although only small proportions of genetic variance have been explained thus far and therapeutic applications will require substantial further effort. Study design issues, power, and limitations are discussed. For psychiatric disorders, there are initial significant findings for common SNPs and for rare copy number variants, and many other studies are in progress. Conclusions: GWAS of large samples have detected associations of common SNPs and of rare copy number variants with psychiatric disorders. More findings are likely, since larger GWAS samples detect larger numbers of common susceptibility variants, with smaller effects. The Psychiatric GWAS Consortium is conducting GWAS meta-analyses for schizophrenia, bipolar disorder, major depressive disorder, autism, and attention deficit hyperactivity disorder. Based on results for other diseases, larger samples will be required. The contribution of GWAS will depend on the true genetic architecture of each disorder.

Effect of Acute Antidepressant Administration on Negative Affective Bias in Depressed Patients

Abstract: Objective: Acute administration of an antidepressant increases positive affective processing in healthy volunteers, an effect that may be relevant to the therapeutic actions of these medications. The authors investigated whether this effect is apparent in depressed patients early in treatment, prior to changes in mood and symptoms. Method: In a double-blind, placebo-controlled, between-groups randomized design, the authors examined the effect of a single 4-mg dose of the norepinephrine reuptake inhibitor reboxetine on emotional processing. Thirty-three depressed patients were recruited through primary care clinics and the community and matched to 31 healthy comparison subjects. Three hours after dosing, participants were given a battery of emotional processing tasks comprising facial expression recognition, emotional categorization, and memory. Ratings of mood, anxiety, and side effects were also obtained before and after treatment. Results: Depressed patients who received placebo showed reduced recogniti...

Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study.

Abstract: Objective: The authors sought to assess the longitudinal course of youths with bipolar spectrum disorders over a 4-year period. Method: At total of 413 youths (ages 7–17 years) with bipolar I disorder (N=244), bipolar II disorder (N=28), and bipolar disorder not otherwise specified (N=141) were enrolled in the study. Symptoms were ascertained retrospectively on average every 9.4 months for 4 years using the Longitudinal Interval Follow-Up Evaluation. Rates and time to recovery and recurrence and week-by-week symptomatic status were analyzed. Results: Approximately 2.5 years after onset of their index episode, 81.5% of the participants had fully recovered, but 1.5 years later 62.5% had a syndromal recurrence, particularly depression. One-third of the participants had one syndromal recurrence, and 30% had two or more. The polarity of the index episode predicted that of subsequent episodes. Participants were symptomatic during 60% of the follow-up period, particularly with subsyndromal symptoms of depression...

Adult Outcomes of Youth Irritability: A 20-Year Prospective Community-Based Study

Abstract: Objective: Irritability is a widely occurring DSM-IV symptom in youths. However, little is known about the relationship between irritability in early life and its outcomes in mid-adulthood. This study examines the extent to which youth irritability is related to adult psychiatric outcomes by testing the hypothesis that it predicts depressive and generalized anxiety disorders. Method: The authors conducted a longitudinal community-based study of 631 participants whose parents were interviewed when participants were in early adolescence (mean age=13.8 years [SD=2.6]) and who were themselves interviewed 20 years later (mean age=33.2 years [SD=2.9]). Parent-reported irritability in adolescence was used to predict self-reported psychopathology, assessed by standardized diagnostic interview at 20-year follow-up. Results: Cross-sectionally, irritability in adolescence was widely associated with other psychiatric disorders. After adjustment for baseline emotional and behavioral disorders, irritability in adolesce...

The Conceptual Development of DSM-V

Abstract: Over the past 30 years, there has been a continuous testing of multiple hypotheses that are inherent in the Diagnostic and Statistical Manual of Mental Disorders, from the third edition (DSM-III) (1) to the fourth (DSM-IV) (2). Although DSM-III was the first official classification of APA to embrace these hypotheses, their intellectual origin is more properly attributed to Eli Robins and Samuel Guze's landmark 1970 article on the establishment of diagnostic validity in psychiatric illness (3) and the subsequent 1972 release of the St. Louis \" Feighner diagnostic criteria \" (4). These formed the basis for the 1978 Research Diagnostic Criteria (RDC) (5), which were used in the longitudinal collabora-tive study on the psychobiology of depression supported by the National Institute of Mental Health (NIMH) (6) and ultimately were the prototypical diagnoses adopted in DSM-III in 1980. The expectation of Robins and Guze (3) was that each clinical syndrome described in the Feighner criteria (4), RDC (5), and DSM-III (1) would ultimately be validated by its separation from other disorders, common clinical course, genetic aggregation in families , and further differentiation by future laboratory tests—which would now include anatomical and functional imaging, molecular genetics, pathophysiological variations, and neuropsychological testing. To the original vali-dators Kendler (7) added differential response to treatment, which could include both pharmacological and psychotherapeutic interventions. After almost 40 years of testing these hypotheses , we are impressed by the remarkable advances in research and clinical practice that were facilitated by having explicit diagnostic criteria that produced greater reliability in diagnosis across clinicians and research investigators in many countries. The benefit of using explicit criteria to increase reliability in the absence of etio-logical understanding was an outcome predicted by the British psychiatrist Ervin Sten-gel (8). However, as these criteria have been tested in multiple epidemiological, clinical, and genetic studies through slightly revised DSM-III-R (9) and DSM-IV editions, the lack of clear separation of these syndromes became apparent from the high levels of co-morbidity that were reported (10, 11). A particularly clear discussion of the inability to identify \" zones of rarity \" between mental disorders was presented by Kendell and Jablensky (12). In addition, treatment response became less specific as selective seroto-nin reuptake inhibitors were found to be effective for a wide range of anxiety, mood, and eating disorders and atypical antipsychotics received indications for schizophrenia, bi-polar disorder, and treatment-resistant major depression. More recently, it was found that …

Exploring the convergence of posttraumatic stress disorder and mild traumatic brain injury.

Abstract: The authors examine the relationship of the two signature injuries experienced by military personnel serving in Afghanistan and Iraq: posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mild TBI). Studies show that a substantial minority of those serving develop persistent emotional sequelae (such as PTSD and other psychological health problems) and/or somatic or cognitive sequelae (postconcussive symptoms) of traumatic exposure. Remarkably, the mechanism (emotional versus biomechanical) and locus (head versus other regions) of injury are weak determinants of whether an individual develops PTSD, persistent postconcussive symptoms, or both. Preexisting or traumatically acquired cognitive dysfunction can increase the risk for these syndromes, probably by reducing cognitive reserve. Structural and functional neuroimaging studies can be interpreted to explain part of the shared symptomatic and functional variance in these syndromes, but this literature is far from consistent and serves mainly to raise new, challenging questions about mutual pathophysiology. The frequent confluence of PTSD and persistent postconcussive symptoms in military personnel strains the bounds of these constructs. New studies are needed to improve our understanding of how emotional and biomechanical stressors can yield these adverse outcomes and how such outcomes can be prevented and treated.

Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia (American Journal of Psychiatry (2009) DOI: 10.1176/appi.ajp.2009. 08050757)

Abstract: OBJECTIVE Impaired verbal memory in schizophrenia is a key rate-limiting factor for functional outcome, does not respond to currently available medications, and shows only modest improvement after conventional behavioral remediation. The authors investigated an innovative approach to the remediation of verbal memory in schizophrenia, based on principles derived from the basic neuroscience of learning-induced neuroplasticity. The authors report interim findings in this ongoing study. METHOD Fifty-five clinically stable schizophrenia subjects were randomly assigned to either 50 hours of computerized auditory training or a control condition using computer games. Those receiving auditory training engaged in daily computerized exercises that placed implicit, increasing demands on auditory perception through progressively more difficult auditory-verbal working memory and verbal learning tasks. RESULTS Relative to the control group, subjects who received active training showed significant gains in global cognition, verbal working memory, and verbal learning and memory. They also showed reliable and significant improvement in auditory psychophysical performance; this improvement was significantly correlated with gains in verbal working memory and global cognition. CONCLUSIONS Intensive training in early auditory processes and auditory-verbal learning results in substantial gains in verbal cognitive processes relevant to psychosocial functioning in schizophrenia. These gains may be due to a training method that addresses the early perceptual impairments in the illness, that exploits intact mechanisms of repetitive practice in schizophrenia, and that uses an intensive, adaptive training approach.

Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes.

Abstract: Objective: Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. Method: This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure wa...

Using Neuroplasticity-Based Auditory Training to Improve Verbal Memory in Schizophrenia

Abstract: Objective: Impaired verbal memory in schizophrenia is a key rate-limiting factor for functional outcome, does not respond to currently available medications, and shows only modest improvement after conventional behavioral remediation. The authors investigated an innovative approach to the remediation of verbal memory in schizophrenia, based on principles derived from the basic neuroscience of learning-induced neuroplasticity. The authors report interim findings in this ongoing study. Method: Fifty-five clinically stable schizophrenia subjects were randomly assigned to either 50 hours of computerized auditory training or a control condition using computer games. Those receiving auditory training engaged in daily computerized exercises that placed implicit, increasing demands on auditory perception through progressively more difficult auditory-verbal working memory and verbal learning tasks. Results: Relative to the control group, subjects who received active training showed significant gains in global cognition, verbal working memory, and verbal learning and memory. They also showed reliable and significant improvement in auditory psychophysical performance; this improvement was significantly correlated with gains in verbal working memory and global cognition. Conclusions: Intensive training in early auditory processes and auditory-verbal learning results in substantial gains in verbal cognitive processes relevant to psychosocial functioning in schizophrenia. These gains may be due to a training method that addresses the early perceptual impairments in the illness, that exploits intact mechanisms of repetitive practice in schizophrenia, and that uses an intensive, adaptive training approach.

Institutional rearing and psychiatric disorders in Romanian preschool children.

Abstract: Objective: There is increasing interest in the relations between adverse early experiences and subsequent psychiatric disorders. Institutional rearing is considered an adverse caregiving environment, but few studies have systematically examined its effects. This study aimed to determine whether removing young children from institutional care and placing them with foster families would reduce psychiatric morbidity at 54 months of age. Method: Young children living in institutions in Bucharest were enrolled when they were between 6 and 30 months of age. Following baseline assessment, 136 children were randomly assigned to care as usual (continued institutional care) or to removal and placement in foster care that was created as part of the study. Psychiatric disorders, symptoms, and comorbidity were examined by structured psychiatric interviews of caregivers of 52 children receiving care as usual and 59 children in foster care when the children were 54 months of age. Both groups were compared to 59 typicall...

Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response.

Abstract: Objective: The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Method: Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Results: Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. Conclusions: These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.

Reducing Suicidal Ideation and Depression in Older Primary Care Patients: 24-Month Outcomes of the PROSPECT Study

Abstract: Objective: The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) evaluated the impact of a care management intervention on suicidal ideation and depression in older primary care patients. This is the first report of outcomes over a 2-year period. Method: Study participants were patients 60 years of age or older (N=599) with major or minor depression selected after screening 9,072 randomly identified patients of 20 primary care practices randomly assigned to provide either the PROSPECT intervention or usual care. The intervention consisted of services of 15 trained care managers, who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 24 months. Results: Compared with patients receiving usual care, those receiving the intervention had a higher likelihood of receiving antidepressants and/or psychotherapy (84.9%–89% versus 49%–62%) and had a 2.2 times greater decline in suicidal ideation over 24 months. Treatment response occurre...

The incidence and course of depression in bereaved youth 21 months after the loss of a parent to suicide, accident, or sudden natural death.

Abstract: Objective: This study examined effects of bereavement 21 months after a parent’s death, particularly death by suicide. Method: The participants were 176 offspring, ages 7–25, of parents who died by suicide, accident, or sudden natural death. They were assessed 9 and 21 months after the death, along with 168 nonbereaved subjects. Results: Major depression and alcohol or substance abuse 21 months after the parent’s death were more common among bereaved youth than among comparison subjects. Offspring with parental suicide or accidental death had higher rates of depression than comparison subjects; those with parental suicide had higher rates of alcohol or substance abuse. Youth with parental suicide had a higher incidence of depression than those bereaved by sudden natural death. Bereavement and a past history of depression increased depression risk in the 9 months following the death, which increased depression risk between 9 and 21 months. Losing a mother, blaming others, low self-esteem, negative coping, ...

Disorder-Specific Dissociation of Orbitofrontal Dysfunction in Boys With Pure Conduct Disorder During Reward and Ventrolateral Prefrontal Dysfunction in Boys With Pure ADHD During Sustained Attention

Abstract: Objective: Among children, attention deficit hyperactivity disorder (ADHD) and conduct disorder are often comorbid and overlap clinically. Neuropsychological evidence suggests that children with conduct disorder demonstrate more prominent motivational problems and children with ADHD demonstrate more prominent attention deficits relative to healthy comparison subjects. The purpose of the present study was to investigate disorder-specific abnormalities in the neurobiological correlates of motivation and sustained attention in children and adolescents with pure conduct disorder and children and adolescents with pure ADHD. Method: Participants were male pediatric patients, ages 9–16 years, with noncomorbid conduct disorder (N=14) and noncomorbid ADHD, combined hyperactive-inattentive subtype (N=18), as well as age- and IQ-matched healthy comparison subjects (N=16). Both patient groups were medication naive. Event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation during ...

The epidemiology of at-risk and binge drinking among middle-aged and elderly community adults: National Survey on Drug Use and Health.

Abstract: Objective: The purpose of this article was to estimate the prevalence, distribution, and correlates of at-risk alcohol use (especially binge drinking) among middle-aged and elderly persons in the United States and to compare at-risk alcohol use between women and men Method: Secondary analysis of the 2005 and 2006 National Survey on Drug Use and Health was conducted for 10,953 respondents aged 50 years and older Among respondents, 6,717 were 50 to 64 years of age and 4,236 were ≥65 years Social and demographic variables, alcohol use (including at-risk use), binge drinking, serious psychological distress, and self-rated health were assessed Results: Overall, 66% of male respondents and 55% of female respondents reported alcohol use during the past year At-risk alcohol use and binge drinking were more frequent among respondents 50 to 64 years of age relative to respondents aged 65 years or older In the ≥65 years old age group, 13% of men and 8% of women reported at-risk alcohol use, and more than 14% o

Manic Symptoms During Depressive Episodes in 1,380 Patients With Bipolar Disorder: Findings From the STEP-BD

Abstract: Objective: Little is known about how often bipolar depressive episodes are accompanied by subsyndromal manic symptoms in bipolar I and II disorders. The authors sought to determine the frequency and clinical correlates of manic symptoms during episodes of bipolar depression. Method: From among 4,107 enrollees in the National Institute of Mental Health’s Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 1,380 individuals met criteria for bipolar I or II depressive syndromes at the time of enrollment and were assessed for concomitant manic symptoms. Illness characteristics were compared in patients with pure bipolar depressed episodes and those with mixed depressive presentations. Results: Two-thirds of the subjects with bipolar depressed episodes had concomitant manic symptoms, most often distractibility, flight of ideas or racing thoughts, and psychomotor agitation. Patients with any mixed features were significantly more likely than those with pure bipolar depressed episodes to hav...

Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: A randomized, double-blind trial of olanzapine versus low doses of haloperidol (American Journal of Psychiatry (2004) 161, (985-995))

Abstract: OBJECTIVE The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis. METHOD Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment. RESULTS An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine. CONCLUSIONS Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.

Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus.

Abstract: Objective: Use of antidepressants has been reported to cause considerable weight gain. The aim of this study was to assess the risk of diabetes mellitus associated with antidepressant treatment and to examine whether the risk is influenced by treatment duration or daily dose. Method: This was a nested case-control study in a cohort of 165,958 patients with depression who received at least one new prescription for an antidepressant between January 1, 1990, and June 30, 2005. Data were from from the U.K. General Practice Research Database. Patients were at least 30 years of age and without diabetes at cohort entry. Results: A total of 2,243 cases of incident diabetes mellitus and 8,963 matched comparison subjects were identified. Compared with no use of antidepressants during the past 2 years, recent long-term use (>24 months) of antidepressants in moderate to high daily doses was associated with an increased risk of diabetes (incidence rate ratio=1.84, 95% CI=1.35–2.52). The magnitude of the risk was simil...